Thymic Stromal Lymphopoetin-Induced Expression of the Endogenous Inhibitory Enzyme SLPI Mediates Recovery from Colonic Inflammation

被引：99

作者：

Reardon, Colin ^{[1
]}

Lechmann, Matthias ^{[1
]}

Bruestle, Anne ^{[1
]}

Gareau, Melanie G. ^{[2
]}

Shuman, Naomi ^{[1
]}

Philpott, Dana ^{[3
]}

Ziegler, Steven F. ^{[4
]}

Mak, Tak W. ^{[1
]}

机构：

[1] Univ Hlth Network, Ontario Canc Inst, Campbell Family Canc Res Inst, Toronto, ON M5G 2C1, Canada

[2] Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada

[3] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada

[4] Benaroya Res Inst Virginia Mason, Seattle, WA 98101 USA

来源：

IMMUNITY | 2011年 / 35卷 / 02期

基金：

加拿大健康研究院;

关键词：

NF-KAPPA-B; SECRETORY LEUKOPROTEASE INHIBITOR; INTESTINAL IMMUNE HOMEOSTASIS; DENDRITIC CELLS; EPITHELIAL-CELLS; EXPERIMENTAL COLITIS; PRIMARY CULTURES; T-CELLS; TSLP; MICE;

D O I：

10.1016/j.immuni.2011.05.015

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Thymic stromal lymphopoetin (TSLP) influences numerous immune functions, including those in the colonic mucosa. Here we report that TSLP-deficient (Tslp(-/-)) mice did not exhibit increased inflammation during dextran sodium sulfate (DSS)-induced colitis but failed to recover from disease, resulting in death. Increased localized neutrophil elastase (NE) activity during overt inflammation was observed in Tslp(-/-) mice and was paralleled by reduced expression of an endogenous inhibitor, secretory leukocyte peptidase inhibitor (SLPI). Pharmacological inhibition of NE or treatment with rSLPI reduced DSS-induced mortality in Tslp(-/-) mice. Signaling through TSLPR on nonhematopoietic cells was sufficient for recovery from DSS-induced colitis. Expression of the receptor occurred on intestinal epithelial cells (IEC), with stimulation inducing SLPI expression. Therefore, TSLP is critical in mediating mucosal healing after insult and functions in a nonredundant capacity that is independent of restraining T helper 1 (Th1) and Th17 cell cytokine production.

引用

页码：223 / 235

页数：13

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